(4R,4aS,7S,7aR,12bS)-3-(cyclopropylmethyl)-4a,7-dihydroxy-9-methoxy-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7-carbaldehyde | 1108714-88-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: (4R,4aS,7S,7aR,12bS)-3-(cyclopropylmethyl)-4a,7-dihydroxy-9-methoxy-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7-carbaldehyde
• CAS: 1108714-88-0
• 化学式: C₂₂H₂₇NO₅
• 分子量: 385.46
• InChiKey: SZXLHRXZPXXELG-DENWASCKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  79.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4R,4aS,7S,7aR,12bS)-3-(cyclopropylmethyl)-4a,7-dihydroxy-9-methoxy-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7-carbaldehyde 、 在 camphor-10-sulfonic acid 作用下， 以 氯仿 为溶剂， 以16%的产率得到
  参考文献：
  名称：

  Synthesis of novel triplet drugs with 1,3,5-trioxazatriquinane skeletons and their pharmacologies. 1: Synthesis of triplet drugs with morphinan skeletons

  摘要：

  We synthesized symmetrical and nonsymmetrical triplet drugs with 1,3,5-trioxazatriquinane skeletons. The isolation of key intermediates, oxazoline dimers, made it possible to effectively produce nonsymmetrical triplets. Among the synthesized triplets, KNT-93, composed of three identical opioid mu receptor agonists, showed dose-dependent antinociception via the mu receptor. The effect was 56-fold more potent than that of morphine, a representative mu agonist. The profound analgesic effect induced by KNT-93 might result from simultaneous occupation of three mu opioid receptors. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.134
• 作为产物：
  描述：

  17-(cyclopropylmethyl)-4,5α-epoxy-6α,14-dihydroxy-3-methoxy-6β-(dimethoxymethyl)morphinan 在 盐酸 作用下， 以 水 为溶剂， 生成 (4R,4aS,7S,7aR,12bS)-3-(cyclopropylmethyl)-4a,7-dihydroxy-9-methoxy-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7-carbaldehyde
  参考文献：
  名称：

  使用新的重排反应合成具有氧杂双环[3.2.1]辛烷骨架的新型阿片样物质配体

  摘要：

  制备具有1,3,5-三氧杂氮杂三喹烷骨架的三聚体的尝试导致发现了新的重排反应，该反应提供了具有氧杂环[3.2.1]辛烷骨架的化合物，提出了其反应机理。基于这种机理，我们以优异的收率从二甲基乙缩醛中间体合成了重排产物。具有氧杂双环[3.2.1]辛烷骨架的化合物显示出对μ和κ的高亲和力，但对δ阿片受体类型没有亲和力。该化合物有望成为新型κ选择性配体的关键中间体。

  DOI：

  10.1016/j.bmcl.2009.03.068

文献信息

• Novel Synthesis of a 1,3,5-Trioxazatriquinane Skeleton Using a Nitrogen Clamp
  作者：Hiroshi Nagase、Akio Watanabe、Masaya Harada、Mayumi Nakajima、Ko Hasebe、Hidenori Mochizuki、Kenji Yoza、Hideaki Fujii

  DOI：10.1021/ol8024988

  日期：2009.2.5

  An α-hydroxyaldehyde derived from naltrexone was converted to an oxazoline dimer with ammonium chloride and sodium acetate in MeOH under reflux. The resulting dimer was treated with dl-camphorsulfonic acid in CHCl3 to give the trimer. The method for trimer synthesis was also applied to general α-hydroxyaldehydes to afford trimers in good yield.

  用氯化铵和乙酸钠在MeOH中的溶液在回流下将衍生自纳曲酮的α-羟醛转化为恶唑啉二聚体。将所得的二聚体在CHCl 3中用dl-樟脑磺酸处理，得到三聚体。三聚体合成的方法也适用于一般的α-羟基醛，以良好的收率得到三聚体。
• Synthesis of novel twin drug consisting of 8-oxaendoethanotetrahydromorphides with a 1,4-dioxane spacer and its pharmacological activities: μ, κ, and putative ε opioid receptor antagonists
  作者：Hideaki Fujii、Akio Watanabe、Toru Nemoto、Minoru Narita、Kan Miyoshi、Atsushi Nakamura、Tsutomu Suzuki、Hiroshi Nagase

  DOI：10.1016/j.bmcl.2008.11.050

  日期：2009.1

  A twin drug consisting of 8-oxaendoethanotetrahydromorphides with a 1,4-dioxane spacer, NS29, was synthesized from a naltrexone derivative. The structure of compound 8, the precursor of NS29, was determined by X-ray crystallography. Monomeric NS28 showed mu opioid receptor antagonist activity, whereas dimeric NS29, consisting of two NS28 units, showed antagonist activities for mu, kappa, and the putative epsilon opioid receptor agonists. Twin drug NS29 and its derivatives are expected to be unique pharmacological tools for investigation of opioid receptor types (C) 2008 Elsevier Ltd. All rights reserved.